Predictive <i>N</i> -Glycan Signatures of Severe Traumatic Brain Injury in Biofluids Using LC–MS/MS

Traumatic brain injury (TBI) poses a significant global health issue, frequently resulting in persistent and even lifelong cognitive and neurological impairments. Despite remarkable advances in biomarker discovery, significant challenges remain in the accurate diagnosis and prognosis of TBI. Glycosylation, an important post-translational modification of proteins and other biomolecules, plays an essential role in neuronal function and neuroinflammation. However, its contribution to the pathogenesis of TBI has been insufficiently investigated. This study examines changes in <i>N</i>-glycosylation patterns in serum and cerebrospinal fluid (CSF) from individuals with severe traumatic brain injury (sTBI) at various time points postinjury. Employing advanced glycomics methodologies and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 102 <i>N</i>-glycans in serum and 86 <i>N</i>-glycans in CSF, revealing substantial alterations in <i>N</i>-glycan expression, including differential expression of fucosylated and sialylated structures. Elevated fucosylation was observed in serum, whereas decreased fucosylation was found in CSF. Altered sialylation patterns were noted, suggesting glycosylation alterations in neuroinflammatory processes and possible neurodegeneration. Furthermore, our study examined <i>N</i>-glycans with isomeric properties. We identified several isomers that demonstrated potential as a biomarker panel reflective of TBI progression. Overall, these studies offer new insights into systemic and central nervous system-specific glycomic responses following sTBI and emphasize the potential of glycan-based biomarkers for monitoring specific changes as TBI progresses, which could be a possible target for enhanced TBI therapy and enhanced prognosis.